Interest in the rare inositol isomer D-chiro-inositol has been kindled by its discovery in inositol phosphoglycan molecules which mimic certain actins of insulin including in vitro effects on lipid metabolism. In order to determine whether D-chiro-inositol might be important in clinical lipid metabolism in diabetic patients, we measured plasma levels of D-chiro-inositol by negative ion gas chromatography/mass spectrometry and compared them to circulating lipoproteins and other co-variates in a cross-sectional study of 73 diabetics and 42 normal subjects. In a subgroup of 28 relatively insulin-deficient NIDDM subjects with glycohemoglobin greater than 10%, plasma D-chiro-inositol level was positively and linearly correlated with plasma triglycerides and was the strongest independent predictor of plasma triglycerides observed. There was no relation of plasma L-chiro-inositol to plasma triglycerides. Plasma D-chiro-inositol was not related to lipids in non-diabetic subjects . The close statistical association between plasma D-chiro-inositol and plasma triglyceride levels in diabetic subjects suggests that disordered D-chiro-inositol metabolism may be a component of diabetic dyslipidemia.